Significance Continuing our studies on intramembranous absorption, defined as the direct fetalabsorption from the amniotic cavity via fetal membranes and fine vessels on top of the placenta, we have been investigating whether compounds administered into the amniotic cavity could become a method for direct fetal therapy. Objectives We[unreadable]ve chosen to look a lung maturation associated with premature delivery. In the rhesus monkey, we have compare maternal injection (betamethasone(BE) & thyroid releasing factor (TRF)) vs. intraamniotic (IA) injections (BE, thyroid hormone (T4)) to determine which rigime is superior for improving indices of fetal lung maturation. If IA therapy proves superb, future human fetal therapy may be as simple as administering a cocktail of agents at the time of diagnostic amniocentesis for a mother with preterm labor. This year we performed studies on 6 animals, comparing the above groups, and a placebo control group. Amniocenteses were performed on gestational day 125 to collect amniotic fluid for determination of SP-A. After amniocentesis, 2 animals received maternal injections of BE (12 mg) IM repeated in 24 hours, and TRF (400 ug) IV every 6 hours for 24 hours. Two other animals, received BE (1 mg) and T4 (60 ug) injected into the amniotic cavity at the time of amniocentesis. The final 2 animals received a saline injection into the amniotic cavity. 72 hours later, the fetuses were harvested by hysterotomy and necropsied. Results The amniotic fluid SP-A increased by 18.8 1 0.5% (P <0.01) at 72 hour in the IA group while decreasing by 5.9 1 5.0% in the maternally treated animals. Immunohistochemical staining of fetal lung for SP-A was increased in the IA lung tissue as compared to the maternal therapy group and the control group. These preliminary results confirm that AI therapy was more effective at enhancing lung maturation. KEYWORDS fetal therapy